Stage IV: Tumour has spread
PRINCIPLES OF TREATMENT
Treatment must be tailored to the best interests of the patient. While the guidelines on optimal clinical management protocols given in Annex 6 should generally be adhered to, overall assessment of the patient, and differences in availability and
quality of surgery, radiotherapy and medical oncology services, may affect the treatment offered. Invasive cancer should be treated at tertiary referral centres, where the necessary expertise and equipment are available. Additional tests, including those to determine the patient’s
suitability to undergo anaesthesia or major surgery, may be required and may affect treatment selection. In HIV-positive women, the CD4 count may also influence the choice of treatment. Testing for syphilis, and blood tests for haemoglobin and liver and kidney function, must also be done before management can be planned.
Survival rates
The survival rate is expressed as the proportion of women surviving 5 years after receiving treatment. It is determined by both disease stage and treatment given. In countries where therapy is either unavailable or inadequate, survival rates are significantly lower than the optimum.
The following factors influence prognosis:
• the clinical stage of disease at presentation: this is the single most important predictor of long-term survival, along with access to treatment;
• age: survival declines with advancing age;
• lymph node status;
• general health, nutritional status, presence of anaemia;
• degree of immunosuppression.
Primary therapy
Primary therapy may be surgery or radiotherapy, or occasionally a combination of both.
Chemotherapy is not used for primary therapy, but may be given concurrently with radiotherapy. Curative surgery in cervical cancer aims to remove the primary tumour, with all extensions, in a single operation. The operation undertaken will depend on the clinical stage of the tumour and the findings of the surgeon when the operation is in progress.
RECOMMENDATION RECOMMENDATION
Surgery and radiotherapy are the only recommended primary treatment modalities for cervical cancer.
Management cancer Annex
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6 Explaining procedures and obtaining informed consent for treatment
The provider should adapt the explanations found in this chapter and in the practice sheets to individual situations, in order to explain procedures, such as surgery and radiotherapy, in terms the patient and her family can understand. The
general rules for counselling given in Practice Sheet 4 also apply to communication of complex information about treatment. It may be helpful to draw or use pictures to illustrate difficult points. The provider should keep medical terminology to a minimum and explain any technical words that have no local translation.
Women should be given all the information they need about a procedure before it is performed. This should include the possible benefits, risks, potential side-effects and what to do if one or more occur, recovery time, cost, and chance of success. If a woman would like family members to help her make a decision on care, they should be included in the discussion. Providers should follow local and national regulations on obtaining informed consent, as well as hospital regulations regarding the need for a signature or thumbprint on a consent form. At the very least, what was said, who was present, and the woman’s understanding and consent, if given, should be documented in her medical record.
Treatment by stage
Of all cervical cancer patients presenting at multidisciplinary gynaecological assessment clinics in tertiary hospitals in developing countries, only about 5% have microinvasive or early invasive cancer (tumours up to stage IB1/IIA <4 cm in diameter).
These cases are preferably treated with surgery because:
• The surgical procedure and recovery in hospital takes less than 2 weeks.
• The extension of the tumour and completeness of removal can be assessed immediately.
• Ovarian function is retained, which is particularly important for premenopausal patients.
• The patient keeps a functional, elastic, and lubricated vagina.
• Most complications are seen within a few days of the procedure.
Surgery should also be favoured for patients with pelvic inflammatory disease, especially when there is an abscess in or near the uterus (pyometra). Radiotherapy, while having the same high 5–year survival rates as surgery, takes about 6 weeks to
Counselling PS4
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administer, and the total extent of the tumour cannot be evaluated. Sequelae, such as loss of vaginal elasticity (fibrosis), shortening and narrowing (stenosis) and dryness of the vagina, may occur months to years after radiation and may make intercourse painful.
About 80% of all cases are in stage IB2 to stage IIIB, with cervical tumours and parametrial involvement extending towards or up to the pelvic side walls, with or without obstruction of the ureters. These bulky tumours, which may measure 10 cm across, have a cure rate ranging from 30% to 75% when treated with radical radiotherapy. Large stage IIA tumours ( 4 cm or more in diameter) are treated as stage IB2 tumours.
Stage IV tumours are less commonly seen. Stage IVA, with rectal or, less commonly, bladder invasion, accounts for about 10% of cases. Only about 10% of these can be cured, and fistulae between the involved organs and the vagina are frequent. Stage IVB (5% of cases), with distant haematogenous metastases, is incurable by any currently known means. However, effective palliative care can be given in these cases.
If the cancer recurs, it is usually in the two years following treatment. The treatment of recurrent cancer is determined by the extent of disease at recurrence, the disease-free interval, the general condition of the patient, and the primary treatment given.
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6 TREATMENT MODALITIES
Surgery
Curative surgery in cervical cancer aims to remove the primary tumour, with all its extensions, in a single operation. The operation undertaken will depend on the clinical stage of the tumour and the findings of the surgeon when the operation is in progress.
Palliative surgery is usually used to relieve distressing symptoms when radiotherapy has failed or caused complications, such as rectovaginal or vesicovaginal fistulae.
Surgical procedures
The main surgical procedures are radical hysterectomy and pelvic lymphadenectomy, although simple hysterectomy and trachelectomy are indicated in specific cases.
After surgery, the patient is usually discharged from the hospital after 7–10 days, but it may take from 6 to 12 weeks for full recovery.
Trachelectomy
Trachelectomy is the removal of the cervix. Radical trachelectomy includes removal of the parametria and upper vagina in addition to the cervix (Figure 6.8).
Figure 6.8 Tissue removed by radical trachelectomy Figure 6.8 Tissue removed by radical trachelectomy
Radical trachelectomy
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Simple hysterectomy
Simple hysterectomy is the surgical removal of the entire uterus, including the cervix, either through an incision in the lower abdomen, or through the vagina (Figure 6.9). The tubes and ovaries are not routinely removed, but they may be, if they appear abnormal.
Figure 6.9 Removal of the uterus by simple hysterectomy Figure 6.9 Removal of the uterus by simple hysterectomy
Radical hysterectomy
Radical hysterectomy is the surgical removal of the uterus, cervix, and surrounding tissues (parametria), including 2 cm of the upper vagina (Figure 6.10). The removal of as much cancer-free tissue from around the tumour as possible is associated with a much better cure rate. Ovaries are not routinely removed because cervical cancer rarely spreads to the ovaries. In a modified radical hysterectomy, less parametrium is removed than in standard radical hysterectomy (Figure 6.10).
Recovery time is slightly longer than after simple hysterectomy.
Figure 6.10 Radical and modified radical hysterectomy Figure 6.10 Radical and modified radical hysterectomy
Radical hysterectomy
Modified radical hysterectomy
Radical hysterectomy
Simple hysterectomy
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6 It is important to note that, even once the surgery has started, the surgeon may
abandon the procedure. This happens when, before incising the peritoneum, the surgeon notices that there is extensive involvement of pelvic nodes. In this case, the patient should be treated with radiotherapy. The peritoneum needs
to remain intact, because incising the peritoneum when lymph nodes are involved increases the rate of complications associated with radiotherapy. The procedure for, and complications of, simple and radical hysterectomy are detailed in Practice Sheet 15.
Bilateral pelvic lymphadenectomy or nodal dissection
This operation involves the removal of the three groups of lymph nodes in the pelvis, which are often involved in invasive cervical cancer, even in early stages (IA2 onwards).
These nodes are located close to the large blood vessels of the pelvis.
Indications
The specific surgical treatment will depend on the extent of the disease.
Trachelectomy is not a standard procedure, but can be offered to women with microinvasive cancer, who wish to have children in the future. There is increasing evidence that a radical trachelectomy with pelvic lymphadenectomy is a valid procedure for treatment of stage IA2.
Simple hysterectomy is indicated for women with microinvasive cervical cancer of stage IA1 and sometimes IA2. Stage IA2 can be treated with a simple hysterectomy and lymph node dissection, but a modified radical hysterectomy with lymph node dissection is preferred. Hysterectomy is not usually indicated for treatment of high-grade precancerous lesions and carcinoma in situ, which can be treated with simpler outpatient methods, but may be appropriate when there are also other gynaecological problems, such as abnormal uterine bleeding. A desire for sterilization on the part of the patient should not be a reason for hysterectomy.
Radical hysterectomy is performed on women who have invasive cervical cancer, with tumours of up to 4 cm in diameter confined to the cervix, or with very early extension to the vaginal fornices (stages IB1 and IIA). Stage IB1 may not be visible (occult IB1).
Hysterectomy PS15
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Type of provider and level of service
Simple hysterectomy can be performed in a regional or central hospital, by a general or gynaecological surgeon specialized in the treatment of cervical cancer. The operation is performed with general anaesthesia and takes about 2 hours.
Radical hysterectomy is usually performed in a central hospital by a gynaecological surgeon specialized in the treatment of cervical cancer, using general anaesthesia; it takes about 3 hours.
RECOMMENDATION RECOMMENDATION
Surgery for treatment of cervical cancer should be performed only by surgeons with focused training in gynaecological cancer surgery.
Radiotherapy
Radiotherapy plays a central role in the treatment of most invasive cervical cancers.
It is mainly used for cases with bulkier tumours (stages IB and IIA through to IVB) and those with extensive involvement of the lymph nodes seen on laparotomy (without hysterectomy). It is also used to manage cancers in patients who are unable to tolerate general anaesthesia. In addition to its curative role, radiation can also alleviate symptoms, especially bone pain and vaginal bleeding.
How radiotherapy works
Notwithstanding its long history of use, radiotherapy is still often poorly understood by the general public. In radiotherapy, the tumour is treated with ionizing radiation.
Radiation is like a ray of light with higher energy, which is released as the ray penetrates the body, damaging and destroying cancer cells. It also has a smaller effect on rapidly dividing normal cells in the skin, bladder and large bowel, which causes some of the reversible symptoms noted during and immediately after treatment. The person receiving radiotherapy feels no pain at the time it is being given.
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6 Types of radiotherapy
There are two broad groups of radiation treatment, which differ in terms of position of the source of radiation relative to the patient:
• teletherapy, in which the source of radiation is distant from the patient;
• brachytherapy, in which small radioactive sources are placed in cavities within the body.
Curative treatments are based on a combination of pelvic teletherapy and intravaginal brachytherapy. The procedures and possible complications are described in Practice Sheets 16 and 17.
Teletherapy
Teletherapy is also called external beam radiation therapy (EBRT). The origin of the radiation is a shielded head, which has a small opening through which a beam of radiation can pass (Figure 6.11). The beam is aimed at the area of the cervix with cancer and the sites at risk of disease spread. Care must be taken to avoid the bladder and rectum, to protect their function. The treatment is administered in a specialist hospital, and takes place in an enclosed space (therapy bunker). No anaesthesia is needed because the patient feels no pain. Radiation machines weigh many tonnes, and the head can rotate around the treatment table where the patient lies. The head may contain radioactive material, such as cobalt 60, or be a linear accelerator, which accelerates electrons to immense speeds until they hit a target and release their energy as radiation – the same process as a diagnostic X-ray machine.In cervical cancer, the radiation is delivered evenly to the entire pelvic contents, in daily sessions of a few minutes each. Usually four beams are used to deliver the total daily dose. Sessions are given on five days a week for about five weeks. In preparation for this treatment, an image of the pelvis is taken by simulation or computerized tomographic scanning. A computer is then used to plan the treatment. The direction of the beams is verified during the treatment using X-rays.
PS16 Teletherapy PS 17 Brachytherapy
PS 16, 17
Figure 6.11 Application of teletherapy Figure 6.11 Application of teletherapy
patient support couch radiation beam source
movable support system
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Brachytherapy
In brachytherapy, the radiation source is in close contact with the tumour. The radiation sources are placed inside an applicator in the uterus and vaginal vault (intracavitary brachytherapy, Figure 6.12).
The radiation is directed to the cancer on the cervix, uterus, upper vagina and tissue surrounding the cervix (parametria). Care is needed to avoid exposing the bladder and rectum to the radiation, in order to preserve their function as much as possible.
The treatment is given by a team of a radiation oncologist, a medical physicist and a radiation technician in a specialist hospital with the appropriate equipment. The radiation is highest within the applicator and decreases rapidly over a few centimetres distance. The dose rate is the speed of delivery of a radiation dose at a specified point.
Intracavitary brachytherapy can be administered with a low dose rate (LDR), pulsed dose rate (PDR), medium dose rate (MDR) or high dose rate (HDR). The rate used determines the time the patient will be kept in isolation, as well as the total dose to be used, and the number of sessions the patient will have.
The most commonly available brachytherapy devices are LDR and HDR, which have similar effectiveness. Usually, only one of these forms is available in any institution.
The two devices are very different in terms of the need for anaesthesia, time spent in hospital, and number of insertions (Table 6.4). It would be advisable for health workers who will be counselling patients on brachytherapy to attend a treatment session at the referral hospital to understand the sequence of events.
Fig 6.12 Application of intracavitary brachytherapy Fig 6.12 Application of intracavitary brachytherapy
Intracavity therapy
radioactive sources
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Table 6.4: Differences between low-dose-rate and high-dose-rate brachytherapy Table 6.4: Differences between low-dose-rate and high-dose-rate brachytherapy
Low dose rate High dose rate Commencement At completion of teletherapy From the third week of
teletherapy
Hospitalization Inpatient: 2–3 days Outpatient: 1/2 to 2 hours Anaesthesia used
at placement
General anaesthesia Mild sedation
Applications Usually once only From 2 to 8: usually 4
Indications
Teletherapy is indicated when the entire area affected by the cancer cannot be removed by simple or radical hysterectomy. This means that most women with invasive cervical cancer without distant metastases (stages IB to IVA) should be treated with teletherapy.
Brachytherapy is usually used in addition to teletherapy. Its use is mandatory if the intent is to cure cervical cancer. For stages IB1 or lower, if surgery is not possible, brachytherapy can be used as the exclusive treatment.
Provider
Radiotherapy is conducted by a radiation oncologist and a radiotherapy technician with standard radiotherapy training.
RECOMMENDATION RECOMMENDATION
Brachytherapy is a mandatory component of curative radiotherapy of cervical cancer.
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Chemotherapy
Chemotherapy is not a primary mode of treatment for cervical cancer, but it may be used concurrently with surgery or radiation to treat bulky tumours. Cisplatin is the most commonly used drug and is included in WHO’s Model List of Essential Medicines. The benefits of adding cisplatin to radiotherapy in developing country settings has not been proven. Cisplatin increases the toxicity of radiotherapy and may not be well tolerated by patients with poor nutrition, anaemia, impaired renal function or more advanced cancers. Radiotherapy alone is an acceptable option.